Trial Outcomes & Findings for Acetaminophen Before Vaccines for Infants Study (AVIS) (NCT NCT00325819)

NCT ID: NCT00325819

Last Updated: 2017-10-13

Results Overview

Fever, defined as rectal temperature \>=38C within 32 hours of vaccination.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 374 participants
• Primary outcome timeframe: Fever within 32 hours following vaccination
• Results posted on: 2017-10-13

Participant Flow

Recruitment and enrollment took place between May 2006 and September 2009. Children potentially eligible for study participation were identified from the Group Health data systems and parents were mailed a letter providing information on the study.

No significant events followed participant enrollment prior to group assignment.

Participant milestones

Measure	Acetaminophen Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations. Children were to receive a maximum of five doses of the study medication and all doses were to be administered within 24 hours of vaccination. Parents were encouraged to take the bottle of study medication to the vaccination visit, and to give the first dose at that visit, after the child's weight was assessed and within an hour before or after vaccination. Parents were instructed to give subsequent doses a minimum of four hours apart and to give the last dose of study medication no later than 24 hours after vaccination. Following the first dose, each subsequent dose was to be given no earlier than 4 hours following the previous dose. A maximum of five doses of study medication were to be given; the last dose no later than 24 hours after the study vaccination. Study drug was formulated to provide 160 mg of acetaminophen per 5 cc dose.	Placebo Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations. Children were to receive a maximum of five doses of the study medication and all doses were to be administered within 24 hours of vaccination. Parents were encouraged to take the bottle of study medication to the vaccination visit, and to give the first dose at that visit, after the child's weight was assessed and within an hour before or after vaccination. Parents were instructed to give subsequent doses a minimum of four hours apart and to give the last dose of study medication no later than 24 hours after vaccination. Following the first dose, each subsequent dose was to be given no earlier than 4 hours following the previous dose. A maximum of five doses of study medication were to be given; the last dose no later than 24 hours after the study vaccination.
Overall Study STARTED	185	189
Overall Study COMPLETED	176	176
Overall Study NOT COMPLETED	9	13

Reasons for withdrawal

Measure	Acetaminophen Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations. Children were to receive a maximum of five doses of the study medication and all doses were to be administered within 24 hours of vaccination. Parents were encouraged to take the bottle of study medication to the vaccination visit, and to give the first dose at that visit, after the child's weight was assessed and within an hour before or after vaccination. Parents were instructed to give subsequent doses a minimum of four hours apart and to give the last dose of study medication no later than 24 hours after vaccination. Following the first dose, each subsequent dose was to be given no earlier than 4 hours following the previous dose. A maximum of five doses of study medication were to be given; the last dose no later than 24 hours after the study vaccination. Study drug was formulated to provide 160 mg of acetaminophen per 5 cc dose.	Placebo Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations. Children were to receive a maximum of five doses of the study medication and all doses were to be administered within 24 hours of vaccination. Parents were encouraged to take the bottle of study medication to the vaccination visit, and to give the first dose at that visit, after the child's weight was assessed and within an hour before or after vaccination. Parents were instructed to give subsequent doses a minimum of four hours apart and to give the last dose of study medication no later than 24 hours after vaccination. Following the first dose, each subsequent dose was to be given no earlier than 4 hours following the previous dose. A maximum of five doses of study medication were to be given; the last dose no later than 24 hours after the study vaccination.
Overall Study Study product lost in mail	2	1
Overall Study Did not take a dose of study product	4	9
Overall Study Lost to Follow-up	3	3

Baseline Characteristics

Acetaminophen Before Vaccines for Infants Study (AVIS)

Baseline characteristics by cohort

Measure	Acetaminophen n=176 Participants Subjects who were randomized to receive acetaminophen	Placebo n=176 Participants Subjects who were randomized to receive placebo	Total n=352 Participants Total of all reporting groups
Age, Categorical <=18 years	176 Participants n=5 Participants	176 Participants n=7 Participants	352 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	24.8 Weeks STANDARD_DEVIATION 4.7 • n=5 Participants	24.2 Weeks STANDARD_DEVIATION 4.7 • n=7 Participants	24.5 Weeks STANDARD_DEVIATION 4.7 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	95 Participants n=7 Participants	172 Participants n=5 Participants
Sex: Female, Male Male	99 Participants n=5 Participants	81 Participants n=7 Participants	180 Participants n=5 Participants
Region of Enrollment United States	176 participants n=5 Participants	176 participants n=7 Participants	352 participants n=5 Participants

PRIMARY outcome

Timeframe: Fever within 32 hours following vaccination

Population: Temperature values were missing for one subject in the acetaminophen group and two subjects in the placebo group.

Fever, defined as rectal temperature >=38C within 32 hours of vaccination.

Outcome measures

Measure	Acetaminophen n=175 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=174 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Fever >=38C Within 32 Hours of Vaccination.	14 percentage of participants Interval 0.41 to 1.01	22 percentage of participants Interval 0.41 to 1.01

SECONDARY outcome

Timeframe: Fever within 32 hours following vaccination

Population: Temperature values were missing for one subject in the acetaminophen group and two subjects in the placebo group.

Fever, defined as rectal temperature >=39C within 32 hours of vaccination.

Outcome measures

Measure	Acetaminophen n=175 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=174 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Fever >=39C Within 32 Hours of Vaccination.	0 percentage of participants	2 percentage of participants

SECONDARY outcome

Timeframe: At any time during participation in the study

The need for unblinding at any time during the study

Outcome measures

Measure	Acetaminophen n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Study Assignment Unblinded	3 percentage of participants	9 percentage of participants

SECONDARY outcome

Timeframe: Within 32 hours of vaccination.

Telephone calls to the consulting nurse or the child's physician that were made due to concerns regarding an acute illness, fever, or possible vaccine reaction and outpatient, urgent care, and emergency room visits that were for evaluation of an acute illness, fever, or a possible vaccine reaction, within 32 hours of vaccination.

Outcome measures

Measure	Acetaminophen n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Medical Utilization	3 percentage of participants	6 percentage of participants

SECONDARY outcome

Timeframe: Within 32 hours of vaccination

Parents were asked to record level of fussiness (compared with the child's usual) within 32 hours of vaccination, using the categories much less than usual, less than usual, about usual, more than usual, and much more than usual.

Outcome measures

Measure	Acetaminophen n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Infant Fussiness Infant fussiness - About usual or less than usual	42 percentage of participants	38 percentage of participants
Infant Fussiness Infant fussiness-More than or much more than usual	58 percentage of participants	62 percentage of participants
Infant Fussiness Infant fussiness-Much more than usual	10 percentage of participants	24 percentage of participants

SECONDARY outcome

Timeframe: On the night following vaccinations

Parents were asked about their sleep on the night following the vaccinations. They were asked to report whether they slept much less than usual, less than usual, about the usual amount, more than usual, or much more than usual on that night.

Outcome measures

Measure	Acetaminophen n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Parent Time Lost From Sleep Parent sleep - About usual or more than usual	73 percentage of participants	77 percentage of participants
Parent Time Lost From Sleep Parent sleep - Less than or much less than usual	27 percentage of participants	23 percentage of participants
Parent Time Lost From Sleep Parent sleep - Much less than usual	3 percentage of participants	5 percentage of participants

SECONDARY outcome

Timeframe: On the night following vaccinations

Parents were asked about their infant's sleep on the night following the vaccinations. They were asked to report whether their infant slept much less than usual, less than usual, about the usual amount, more than usual, or much more than usual on that night.

Outcome measures

Measure	Acetaminophen n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=176 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Infant Time Lost From Sleep Infant sleep - About usual or more than usual	78 percentage of participants	81 percentage of participants
Infant Time Lost From Sleep Infant sleep - Less than or much less than usual	22 percentage of participants	19 percentage of participants
Infant Time Lost From Sleep Infant sleep - Much less than usual	2 percentage of participants	2 percentage of participants

SECONDARY outcome

Timeframe: Through the day after vaccination

Population: Refers to the number of participants for whom parents reported that they were scheduled to work on the day of the vaccination visit or the day following the child's vaccination visit.

Parents were asked to report whether they were scheduled to work on the day of the vaccination visit (but following that visit) or the next day and, if so, whether they had to miss work to care for their infant because of fever, fussiness, or possible vaccine reaction on those days.

Outcome measures

Measure	Acetaminophen n=143 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.	Placebo n=140 Participants Children were randomized 1:1 to receive up to five doses of acetaminophen (10-15mg per kg) or placebo following routine vaccinations.
Parent Time Lost From Work	4 percentage of participants	1 percentage of participants

Adverse Events

Acetaminophen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Lisa Jackson, MD, MPH

Group Health Research Institute

Phone: 206-442-5216

Email: jackson.L@ghc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place